Hsa_circ_0003528 promotes cell malignant transformation and immune escape via increasing oncogene PDL1 through sponging miR-511-3p in non-small cell lung cancer

Environ Toxicol. 2023 Jun;38(6):1347-1360. doi: 10.1002/tox.23768. Epub 2023 Mar 22.

Abstract

Background: Accumulating evidence suggests that circular RNAs (circRNAs) play important regulatory roles in non-small cell lung cancer (NSCLC). At present, we aimed to explore the regulatory role of has_circ_0003528 (circ_0003528) in NSCLC.

Methods: Alterations of circ_0003528 expression in NSCLC samples and cell lines were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Impacts of circ_0003528 on NSCLC cell malignant transformation were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transwell invasion, and tube formation assays. Epithelial-mesenchymal transition (EMT)-related markers were detected with western blotting. Pro-inflammatory cytokines were detected by Enzyme-linked immunosorbent assay (ELISA). The regulation mechanism of circ_0003528 was verified by dual-luciferase reporter and RNA pull-down assays. The tumorigenesis role of circ_0003528 was verified by animal experiments.

Results: Higher levels of circ_0003528 were obtained in NSCLC samples and cell lines, and patients with high circ_0003528 expression had a worse prognosis. Silence of circ_0003528 decreased xenograft growth in mouse models and induced cell apoptosis and repressed cell viability, proliferation, invasion, EMT, angiogenesis, and immune escape in NSCLC cells in vitro. Mechanistically, circ_0003528 controlled programmed cell death ligand 1 (PDL1) expression through interaction with miR-511-3p. The inhibiting impacts of circ_0003528 knockdown on NSCLC cell malignant transformation and immune escape were weakened after miR-511-3p silencing. Moreover, PDL1 overexpression partially counteracted miR-511-3p upregulation-mediated suppression on NSCLC cell malignant transformation and immune escape.

Conclusions: Circ_0003528 facilitated NSCLC cell malignant transformation and immune escape through regulation of the miR-511-3p/PDL1 axis, highlighting the oncogenic role of circ_0003528 in NSCLC.

Keywords: NSCLC; PDL1; circ_0003528; miR-511-3p.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Mice
  • MicroRNAs* / genetics
  • Oncogenes / genetics

Substances

  • MicroRNAs
  • MIRN511 microRNA, human